The cytochrome P-450's comprise a class of microsomal proteins that are extremely important in the metabolism of xenobiotic compounds, notably carcinogens, mutagens, and teratogens. In most systems examined, their synthesis is inducible, in that administration of substrates leads to greatly increased tissue levels of these proteins. This project will involve studies designed to examine the genetic control of this response in Drosophila metanogaster. Methods for preparation and assay of P-450's will be developed, and the response of these proteins to xenobiotics in the diet will be determined. Using appropriately constructed stocks, we will screen for genetic variants that affect this response. These variants will then be characterized genetically, by means of mapping experiments, biochemically, by means of electrophoresis, protein purification, and immunochemical analysis, and physiologically, especially with respect to the role of inductive responses in affecting in vitro and in vivo mutagen sensitivity. The goal of this project is to exploit the wealth of information available on the genetics of Drosophila in the characterization of the genetic control of these proteins, with the hope that the information so gained can be applied to studies of mammalian systems. Results obtained will be very valuable in helping to understand the role played by these proteins in carcinogenesis and other processes related directly or indirectly to the actions of toxic compounds found in the environment.